This is a proposal from a group of eight NIH funded principal Investigators requesting funds to purchase a commercially available two-Photon microscope system, This .shared Instrument will permit high resolution deep tissue imaging essential for understanding the structure and function of the brain. The requested two-photon only system will provide valuable new Information difficult or impossible to obtain with the traditional Imaging approaches presently available to the neuroscience community at NYU medical school. The proposed studies cover developmental, cellular and system neurobiology projects including: Imaging cortical (projects 1 and 2). Hippocampal (project 3), striatal (project 4) and retinal ganglion neurons (project 5) to study their development, regulation and function;monitoring the formation of Nodes of Ranvier in the CNS In health and disease (project 6);and examining the structural and functional changes of synapses in the living mouse cortex (projects 7-8). The new system provides two key advantages that will be transformative for all the projects presented in this proposal: 1) The instrument permits Imaging up to 400 um deep In tissues and 2) By combining It with an electrophysiological setup It will allow for combined In vivo imaging and electrophysiological studies, The device will be housed In the Smilow Neuroscience Institute, a shared facility close to all eight users'laboratories and will also be available to the research community at New York University as time permits, This device will have long-term Institutional support to cover the service contracts as well as part of the technician's salary. The requested system will greatly facilitate neuroscience research at NYU School of Medicine and will help understand how neural circuits are assembled and function under normal and pathological conditions. PUBLIC HEALTH RELEVANCE: This is a proposal from a group of eight NIH funded principal investigator's requesting funds to purchase a two-photon microscope system for in vivo studies of brain structure and function. With the help of the new imaging system, the proposed studies will lead to a better understanding of how neural circuits are assembled and modified and how they function under normal and pathological conditions. Such knowledge will be critical for developing therapeutic strategies for the treatment of various brain diseases.